Malate synthase (MS)

Malate synthase is a critical enzyme in the glyoxylate cycle, a metabolic pathway that allows plants, bacteria, and fungi to bypass the carbon-dioxide-releasing steps of the tricarboxylic acid (TCA) cycle. It catalyzes the condensation of acetyl-CoA and glyoxylate to produce malate and coenzyme A, facilitating the conversion of fatty acids into carbohydrates (Source: UniProt P9WKK1). This enzyme is particularly significant in the context of infectious diseases, as it is essential for the persistence of Mycobacterium tuberculosis during the latent phase of infection when the pathogen relies on host-derived lipids for survival (Source: PubMed PMID 16321614). Because the glyoxylate cycle is absent in humans, malate synthase represents a promising and highly selective therapeutic target for the development of new antibiotics and antifungals (Source: PubMed PMID 23091060). Small molecule inhibitors, such as phenyl-diketo acid derivatives, are being actively researched to block this metabolic bottleneck and treat multidrug-resistant infections (Source: PubMed PMID 29033324). Therapeutic challenges primarily involve achieving sufficient drug penetration and stability within the host environment to effectively eliminate persistent microbial populations.

Other names

(S)-malate glyoxylate-lyase (CoA-acetylating)Glyoxylate transacetaseMalate synthase GMalate synthase AGlcB

Inhibition of the enzymatic condensation of acetyl-CoA and glyoxylate to form malate, thereby disrupting the glyoxylate shunt and preventing the utilization of two-carbon compounds for energy and biomass.